Finerenone in Type 2 Diabetes with CKD Stage 3–4 and Albuminuria
Add finerenone 10 mg once daily to your patient's current ACE inhibitor or ARB therapy, provided serum potassium is ≤4.8 mmol/L and eGFR is ≥25 mL/min/1.73 m², then uptitrate to 20 mg daily after 1 month if potassium remains ≤4.8 mmol/L. This recommendation is based on the KDIGO 2022 guidelines and robust phase 3 trial evidence showing significant reductions in both kidney disease progression and cardiovascular events 1.
Efficacy Data: Dual Cardiorenal Protection
Kidney Outcomes
- Finerenone reduces composite kidney outcomes by 23% (HR 0.77,95% CI 0.67–0.88) in the pooled FIDELITY analysis, including kidney failure, sustained ≥57% eGFR decline, or renal death 1, 2.
- Progression to end-stage kidney disease is reduced by 36% (HR 0.64,95% CI 0.41–0.995) in patients with more advanced diabetic kidney disease 3.
- In FIDELIO-DKD specifically, the composite kidney outcome (kidney failure, sustained ≥40% eGFR decline, or kidney death) was reduced by 18% (HR 0.82,95% CI 0.73–0.93) 1.
Cardiovascular Outcomes
- Finerenone reduces composite cardiovascular events by 14% (HR 0.86,95% CI 0.78–0.95), including cardiovascular death, nonfatal MI, nonfatal stroke, or hospitalization for heart failure 1, 2.
- Heart failure hospitalizations are reduced by 29% (HR 0.71,95% CI 0.56–0.90), with particular benefit in preventing new-onset symptomatic heart failure 4, 3.
- In FIGARO-DKD, which enrolled patients with less advanced CKD, cardiovascular events were reduced by 13% (HR 0.87,95% CI 0.76–0.98) 3.
These benefits were demonstrated across a broad CKD spectrum with median eGFR 57.6 mL/min/1.73 m² and 67% of patients having severe albuminuria (ACR ≥300 mg/g) 1.
Recommended Dosing Protocol
Initial Dose Selection (eGFR-Based)
- Start 10 mg once daily when eGFR is 25–60 mL/min/1.73 m² (your patient with CKD stage 3–4 qualifies) 4, 5.
- Start 20 mg once daily when eGFR is >60 mL/min/1.73 m² 4, 5.
Uptitration Strategy
- After 1 month, increase from 10 mg to 20 mg daily if both conditions are met 4, 5:
- Serum potassium remains ≤4.8 mmol/L
- eGFR is stable (no clinically significant decline)
This eGFR-based dosing strategy was used in the pivotal FIDELIO-DKD and FIGARO-DKD trials to balance efficacy with hyperkalemia risk 3, 5.
Monitoring Parameters
Pre-Initiation Requirements
- Verify serum potassium ≤4.8 mmol/L before starting therapy 1, 4.
- Confirm eGFR ≥25 mL/min/1.73 m² (do not initiate if <25 mL/min/1.73 m² or on dialysis) 4, 5.
- Document persistent albuminuria (UACR ≥30 mg/g) despite maximum tolerated ACE inhibitor or ARB 1, 4.
Potassium Monitoring Schedule
- Check at 1 month after finerenone initiation to capture the predictable early potassium rise 4, 5.
- Check every 4 months during maintenance therapy 4, 5.
Potassium-Based Management Algorithm
- Potassium ≤4.8 mmol/L: Continue current dose; uptitrate from 10 mg to 20 mg if at 1-month check 4, 5.
- Potassium 4.9–5.5 mmol/L: Continue current dose without adjustment; maintain monitoring every 4 months 4, 5.
- Potassium >5.5 mmol/L: Immediately hold finerenone, evaluate dietary potassium and concomitant medications, recheck potassium levels, and restart at 10 mg daily when potassium returns to ≤5.0 mmol/L 4, 5.
Additional Monitoring
- eGFR: Check at baseline, 1 month, then every 4 months 5.
- UACR: Obtain at baseline and month 4 to evaluate albuminuria response 5.
Contraindications
Absolute Contraindications
- eGFR <25 mL/min/1.73 m² or end-stage renal disease (no established dosing or safety data) 5.
- Baseline serum potassium >4.8 mmol/L (excessive hyperkalemia risk) 4, 5.
Relative Contraindications (Trial Exclusion Criteria)
- Uncontrolled hypertension 5.
- Symptomatic heart failure with reduced ejection fraction was excluded from FIGARO-DKD, though recent FINEARTS-HF data now support use in HFmrEF/HFpEF 6.
Safety Profile and Common Pitfalls
Hyperkalemia Risk
- Hyperkalemia occurs in 14% with finerenone versus 6.9% with placebo, but permanent discontinuation is rare (1.7% vs 0.6% over 3 years) 1, 3, 2.
- No deaths were attributed to hyperkalemia in the pivotal trials 3.
- Risk factors for hyperkalemia include lower eGFR (<45 mL/min/1.73 m²) and beta-blocker use; SGLT2 inhibitor co-administration is protective 5.
Expected Creatinine Changes
- A creatinine rise up to 30% from baseline is an expected hemodynamic effect, not acute kidney injury, reflecting reduced intraglomerular pressure 5.
- Continue finerenone if creatinine rise is <30%, patient is clinically stable, and no volume depletion or nephrotoxin exposure is present 5.
- Hold finerenone if creatinine increase exceeds 30%, volume depletion is present, or acute illness occurs 5.
Critical Pitfalls to Avoid
- Do not start finerenone before optimizing RAS inhibitor therapy—patients must be on maximum tolerated ACE inhibitor or ARB dose first 3, 5.
- Do not permanently discontinue for a single potassium >5.5 mmol/L episode—temporary interruption with dose reduction upon restart (10 mg daily) successfully manages most cases 5.
- Do not mistake hemodynamic creatinine changes for AKI—the absence of volume depletion, nephrotoxin exposure, and clinical instability argues against true kidney injury 5.
- Do not consider SGLT2 inhibitors and finerenone interchangeable—they have complementary mechanisms and can be combined for additive cardiorenal protection 3, 5.
Treatment Sequencing in Diabetic CKD
The KDIGO 2022 guidelines recommend a hierarchical approach 1:
- First-line foundation: Maximum tolerated ACE inhibitor or ARB (already in place for your patient) 1, 4.
- Second-line priority: SGLT2 inhibitor (provides largest effect on renal and cardiovascular outcomes) 1, 4.
- Third-line consideration: Finerenone for persistent albuminuria despite SGLT2 inhibitor, or when SGLT2 inhibitor is contraindicated/not tolerated 1, 4.
Finerenone may be added to both RAS inhibitor and SGLT2 inhibitor for complementary cardiorenal protection in patients with persistent albuminuria 4, 3.